br Introduction The conquest of cancer continues to

Introduction The conquest of cancer continues to pose great challenges to medical science (Reese, 1995; Varmus, 2006; Alberts, 2011; Watson, 2013). There is a compelling need for innovative cancer research integrating biomedical sciences with new technology in order to ultimately conquer cancer. Femtosecond (fs) (1fs=10s) time-resolved laser spectroscopy (fs-TRLS) is a direct technique to visualize molecular reactions in real time. Its application to chemical and biological systems gave birth to the fields of femtochemistry and femtobiology, with the pioneering contribution of Zewail (2000). Further, femtomedicine (FMD), which fuses ultrafast laser spectroscopic techniques with biomedical sciences, was recently coined to advance fundamental understanding and therapies of human diseases notably cancer (Wang et al., 2009; Lu, 2010a; Nguyen et al., 2011). In particular, we proposed that dissociative-electron-transfer (DET) reactions may be exploited to improve cancer therapy (Lu, 2010a; Luo et al., 2012). Prior to our studies in FMD, it had strikingly been found that electron-induced dissociation of halogenated molecules were enhanced by up to 30,000 times with the presence of polar molecules such as NH3 and H2O, and a DET mechanism involving a prehydrated electron (epre−) trapped in polar media was proposed to explain the results (Lu and Madey, 1999; Lu, 2010b). Employing fs-TRLS, we demonstrated that epre− in liquid water has a lifetime of about 500fs and is a weakly-bound excited state of the hydrated/solvated electron (Wang et al., 2008). We further discovered that the epre− plays a key role in causing the biological effects of ionizing radiation: its ultrafast DET reaction leads to chemical bond breaks at the guanine purchase pppa (Wang et al., 2009) and strand breaks in DNA (Nguyen et al., 2011). Our findings challenged the conventional notion that damage to the genome by ionizing radiation is mainly oxidative, induced by oxidizing OH, and might lead to improved strategies for radiotherapy of cancer (Lu, 2010a). We have also discovered the DET mechanism of cisplatin (Lu, 2007; Lu et al., 2007). Platinum compounds as a class of antitumor agents were discovered unexpectedly by the biophysicist Rosenberg et al. (1965, 1969). Despite its severe toxicity (Reese, 1995), cisplatin is a widely-used drug in the treatment of a variety of cancer, including ovarian, testicular, cervical, bladder, lung, head and neck, lymphomas, and brain cancers, both as chemotherapy alone and in combination with radiotherapy. Although platinum compounds are well-known DNA-attacking agents, their precise molecular mechanism of action remained elusive until recently. Through fs-TRLS studies, we found that cisplatin is very effective for the DET reaction with a weakly-bound electron, such as an ultrashort-lived epre− produced by radiolysis of water (Lu, 2007): The resultant cis-Pt(NH3)2Cl and cis-Pt(NH3)2 radicals are highly effectively in inducing DNA strand breaks. For cisplatin as a chemotherapeutic drug, its DET reaction with the G base in DNA was also observed (Lu et al., 2007). This DET mechanism has directly unraveled the radiosensitizing effect of cisplatin (Lu, 2007) and the long-existing mystery why the cisplatin-like drugs result in the preferential binding of the cis-Pt(NH3)2 to two neighboring G bases in DNA (Lu et al., 2007). Other researchers have subsequently confirmed this DET mechanism in experiments and theoretical calculations (Kopyra et al., 2009; Kuduk-Jaworska et al., 2011). Similarly, we also found an ultrafast DET mechanism for a halopyrimidine family (XdUs, X=I, Br and Cl) as potential sensitizers for radiotherapy (Wang et al., 2006; Wang and Lu, 2007, 2010). Using fs-TRLS, we observed directly the ultrafast DET reactions of XdUs with epre−, leading to the formation of the reactive radical (dU•), but they are far less efficient than that of cisplatin, due to the lack of the NH3 groups as the effective electron-transfer promoter (Lu and Madey, 1999; Lu, 2010b), and thus have not sufficient radiosensitizing efficacies.